Biotin-conjugated PEGylated porphyrin self-assembled nanoparticles co-targeting mitochondria and lysosomes for advanced chemo-photodynamic combination therapy

摘要

The combination of chemotherapy and photodynamic therapy (chemo-PDT) has been suggested as an alternative therapy for drug-resistant cancers. In this study, biotin-conjugated PEGylated photosensitizer (PS) self-assembled nanoparticles (meso-tetraphenylporphyrin (TPP)-PEG-biotin SANs) were prepared via a self-assembly process to serve as nanocarriers for chemo-drugs as well as PSs. Electron microscopy results reveal the spherical shape of the nanoparticles (NPs). In the NPs, conjugated biotin plays a key role in selective tumor targeting. In vitro cellular experiments revealed the rapid cellular uptake of the TPP-PEG-biotin conjugates by MCF-7 cells that overexpress the biotin receptor, and verified that the conjugates were much more effective PSs than TPPS used as control in the cytotoxicity test. Interestingly, subcellular localization studies showed that the conjugates and their self-assembled NPs were localized mainly in mitochondria and partially in lysosomes, whereas TPPS was localized only in lysosomes. With the exclusive localization in mitochondria, high-content cell based assay showed that the TPP-PEG-biotin SANs induced rapid mitochondrial membrane potential transition (MPT), leading to cellular apoptosis. The chemo-drug doxorubicin (DOX) was successfully encapsulated in the TPP-PEG-biotin SANs (DOX@TPP-PEG-biotin) and had synergistic effects with enhanced cytotoxicity after PDT action. Collectively, the DOX@TPP-PEG-biotin SANs have promising potential as an effective anticancer agent in targeted combination therapy.